FDA Panel Says OK to New Use for Eye Drug

WASHINGTON -- An FDA advisory committee voted unanimously on Thursday to recommend approval of a new indication for ranibizumab (Lucentis) for the treatment of diabetic macular edema.

The Dermatologic and Ophthalmic Drugs Advisory Committee considered two doses of the drug, which is injected monthly. There was unanimity on the lower 0.3 mg dose; the 0.5 mg dose won members' assent with an 8-2 vote.

The committee also voted 10-0 that there was no difference in efficacy between the two doses; however, the group split 4-4 (with two abstentions) on whether there was a difference in safety. The agency is not obligated to follow the advice of its advisory committees, but often does.

Currently, there are no drugs approved to treat diabetic macular edema. For the past 30 years, it's been treated with laser photocoagulation; however, few patients notice a benefit in vision. Further, the procedure can destroy retinal tissue and decrease sensitivity to color.

Drugmaker Genentech's approval application is based on two randomized, double-blind, sham-controlled studies involving a total of more than 750 patients, according to briefing documents released by FDA in advance of the meeting.

In both studies, participants received injections of either 0.5 mg or 0.3 mg of ranibizumab, or placebo, once a month for 24 months, and were followed for 36 months.

Ranibizumab met its primary endpoint of improving patients' eye chart test score by at least 15 letters after 24 months of treatment. The 0.3-mg dose achieved this in 38.6% of 125 patients (P=0.0001 compared with placebo) and the 0.5-mg dose improved it in 50.0% of patients (P<0.0001). In the placebo group, improvement occurred in 14.4% of patients.

The clinical trial also met its secondary endpoint of patients achieving 20/40 vision, hitting the mark in 54.4% of patients taking the lower dose and 62.2% of those on the higher dose. That endpoint also was reached among 34.6% of patients on placebo.

The reviewers noted a high number of deaths in the ranibizumab treatment arms. In all, 11 patients in the 0.5-mg group died, as did seven patients in the 0.3-mg group and three patients on placebo. The adverse event rates in each group were 36.4%, 32.4%, and 33.2%, respectively.

Specific adverse event rates included:

Myocardial infarction: 2.8% in the 0.5-mg group, 3.6% in the 0.3-mg group, and 3.6% in the placebo group

Pneumonia: 4.0%, 1.6%, 2.8%

Kidney failure: 2.0%, 1.2%, 1.6%

The number of eye-related adverse events were similar in all treatment groups, the reviewers found.

The vote represents "a great day for patients," Tony Adamis, MD, vice-president and global head of ophthalmology for Genentech, told MedPage Today in an interview. "There was a consensus on the committee that Lucentis had a real beneficial impact on patients ... and assuming this medication is approved, it would have a real impact on patients' lives."

Adamis said he viewed the split vote on safety of the higher dose as "not so much a concern for adverse events as [it was that] both doses had identical efficacy, so the most conservative thing to do is offer up a lower dose to minimize exposure to the drug."

He said the company is looking at other uses for ranibizumab, focusing on "long-acting technologies so patients don't have to come in and get treated as frequently."

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